PACES: Protein sequential assignment by computer-assisted exhaustive search
PACES: Protein sequential assignment by computer-assisted exhaustive search
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DOI：
10.1023/a:1023589029301
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发表时间：
2003-06-01
影响因子：
2.7
通讯作者：
Zhou, P
中科院分区：
文献类型：
--
作者：
Coggins, BE;Zhou, P
使用核磁共振（NMR）光谱确定蛋白质溶液结构的关键步骤是顺序分配过程，该过程将骨架共振与蛋白质一级序列中的相应残基相关联，目前通常使用来自三重共振NMR实验的数据。虽然自动化的顺序分配方法的发展大大促进了这一过程，这些程序的性能通常是不太令人满意的大蛋白质，特别是在缺少连接或严重的化学位移简并的情况下。在这里，我们报告了一种新的计算机辅助顺序分配方法的发展，使用一种算法，进行穷举搜索的所有自旋系统都建立顺序连接，然后分配。通过在每个周期之后在用户干预的情况下迭代地运行程序，可以有效地消除分配中的模糊性，并且可以快速地分配骨干共振。这种方法的效率和鲁棒性进行了测试，与27个蛋白质的大小从76个氨基酸到723个氨基酸不等，并与不同质量的数据，使用实验数据的三种蛋白质，并公布的任务修改与模拟噪声的其他24。顺序分配的蛋白质的大小，NMR数据集的完整性，和共振位置的不确定性方面的复杂性进行了检查。
A crucial step in determining solution structures of proteins using nuclear magnetic resonance (NMR) spectroscopy is the process of sequential assignment, which correlates backbone resonances to corresponding residues in the primary sequence of a protein, today, typically using data from triple-resonance NMR experiments. Although the development of automated approaches for sequential assignment has greatly facilitated this process, the performance of these programs is usually less satisfactory for large proteins, especially in the cases of missing connectivity or severe chemical shift degeneracy. Here, we report the development of a novel computer-assisted method for sequential assignment, using an algorithm that conducts an exhaustive search of all spin systems both for establishing sequential connectivities and then for assignment. By running the program iteratively with user intervention after each cycle, ambiguities in the assignments can be eliminated efficiently and backbone resonances can be assigned rapidly. The efficiency and robustness of this approach have been tested with 27 proteins of sizes varying from 76 amino acids to 723 amino acids, and with data of varying qualities, using experimental data for three proteins, and published assignments modified with simulated noise for the other 24. The complexity of sequential assignment with regard to the size of the protein, the completeness of NMR data sets, and the uncertainty in resonance positions has been examined.